1. Field of the Invention
This invention relates generally to antibiotic compositions comprising rifampin, of a type which is orally administerable, and particularly to a composition of such type which is aqueously homogenizable with low foaming.
2. Description of the Related Art
Rifampin is a semi-synthetic antibiotic which has been widely used in pharmaceutical applications, particularly as an antibacterial and antitubercular compound.
Although highly useful as an antibiotic in these application areas, rifampin has the inherent disadvantage that it is poorly soluble in water, being only slightly soluble at a pH below 6. As a result, the physiological availability of such compound, especially at the higher pH values present in the lower gastrointestinal system, is poor.
This solubility problem has been recognized in the art, and various additives have been proposed to overcome such deficiency, as noted in U.S. Pat. No. 4,613,496 to Helmut Kopf, et al, with reference to Japanese Patent Disclosure No. SHO 53-1333624 of Nov. 21, 1978. Among the additives described in the Japanese reference for overcoming such poor solubility characteristics are sodium lauryl sulfate, a sucrose fatty acid ester, a sorbitan fatty acid ester, dioctyl sulfosuccinate, fillers such as lactose, D-mannitol, and corn starch, and lubricants such as calcium stearate. The resulting compositions are said by the U.S. patent to exhibit unsatisfactory to poor elution properties at a pH of 3.
Also described in the U.S. patent to Kopf et al are mixtures of rifampin with crystalline cellulose, alone or with polyoxylol 40 stearate, polysorbate 80, glycerol monostearate, hydroxypropyl cellulose, or hydroxypropyl methylcellulose, with magnesium stearate present in all instances as a lubricant. Such mixtures are disclosed as having satisfactory elution properties at a pH of 3.
The specific improvement in rifampin soluble compositions in U.S. Pat. No. 4,613,496 is the provision of a composition containing a mixture of from about 75 to about 90 percent of rifampin, from about 5 to about 20 percent of crystalline cellulose, about 0.05 to about 5 percent of sodium lauryl sulfate, and about 0.5 to about 5 percent of a pharmaceutically acceptable lubricant, e.g., magnesium stearate. Such composition is disclosed as having uniform and complete dissolution rates in both acidic media simulating the conditions of the normal and healthy human stomach and the neutral to slightly basic medium simulating abnormal human stomach conditions, as well as those of the lower gastrointestinal tract. As a result, the disclosed composition of this patent is said therein to exhibit a dissolution rate which is virtually independent of the surrounding pH conditions and which guarantees a consistently uniform and for all practical purposes a complete availability of the active ingredient (rifampin).
The rifampin composition disclosed in the above-described Kopf et al patent is described as a solid pharmaceutical composition primarily useful for oral administration, e.g., in the form of an uncoated or coated tablet, or a capsule.
While the rifampin composition disclosed in the Kopf et al patent is described as having superior overall elution characteristics in the analytical test (column dissolution rate test) referenced at column 2, lines 26-33 of the patent, as simulative of physiological environments in which the drug may be employed, it nonetheless is true that in vivo the rifampin in aqueous physiological media will have a high degree of foaming character, and such foaming will significantly adversely affect the bioavailability of rifampin therein.
It therefore is an object of the present invention to provide a rifampin composition which is aqueously homogenizable with low foaming.
It is another object of the invention to provide such a composition in a form which is orally administerable, either in solid form such as tablets or capsules, or in an aqueous carrier medium.
It is a further object of the invention to provide a method of antibiotic treatment using such rifampin composition.
Other objects and advantages will be more fully apparent from the ensuing disclosure and appended claims.